To objectify the extent of asymmetric inter-eye progression in Stargardt disease (STGD1).

Methods

Eighty-five STGD1 patients were selected based on the presence of follow-up data on fundus autofluorescence (FAF). We identified 12 out of these 85 patients who carried at least 1 ABCA4 mutation and showed yellow fundus flecks, but with differences in the size of atrophic retinal pigment epithelium lesions between their eyes. Inter-eye comparisons were performed with paired-samples T-tests using visual acuity (VA), fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). The inter-eye differences in progression is evaluated with VA and geographic atrophy (GA) on FAF.

Results

BASELINE: The mean age was 49.5 years (±standard deviation 13.2, range: 26-69). The mean VA in the best and worst eyes were 0.32 logMAR (±0.30; Snellen 20/42) and 0.75 logMAR (±0.49; Snellen 20/112), respectively. The mean GA-regions were 0.77 mm² (±1.31) and 4.40 mm² (±5.18), respectively. The mean transverse losses of the ellipsoid zone (EZ-loss) on SD-OCT were 2242 µm (±981) and 3182 µm (±859), respectively. Inter-eye differences for VA, GA and EZ-loss were significant (P=0.018; P=0.011; P=0.003).<br /> FOLLOW-UP: The mean follow-up time was 4.1 years (±2.8, range: 0.5-8.3). The mean progression rates for VA in the best and worst eyes were 0.05 logMAR/year (±0.08; range: -0.13-0.17) and 0.12 logMAR/year (±0.19; range: -0.11-0.50), respectively. The mean progression rates for GA were 0.36 mm²/year (±0.43; range: 0-1.43) and 0.99 mm²/year (±0.67; range: 0.29-2.84), respectively. The differences in progression speed were significant for GA (P=0.0004), but not for VA (P=0.254).

Conclusions

We found remarkable inter-eye differences in 14% (12/85) of this patient cohort. Moreover, the progression speed of GA is likely to be faster in the worst eye, resulting in a further increase of the asymmetry as the disease progresses. Such results are unlikely to be found in inherited retinal dystrophies, owing to the nature of these diseases. However, in light of future therapeutic trials for STGD1, asymmetry at baseline should be excluded if fellow eyes serve as the control group. When they are included, they could mask potential effects when the worst eye is treated.